The smell test that could stop Parkinson’s disease

By Maurice Curtis

In the Western world over the past 60 years, we’ve added about 15 years to our average lifespan. That’s a success story. The downside is that as the population lives longer, neurological diseases have become a major problem globally.

The brain is the most complex organ in the body, and many people now live long enough to experience that remarkable organ starting to fail.

One in five New Zealanders will face a disease affecting their brain at some stage of their life.

To me, understanding the human brain is the final frontier of human knowledge. But the ultimate goal is to be able to fix the brain when neurological diseases, such as Parkinson’s, strike.

More than 12,000 people in New Zealand suffer from Parkinson’s. It causes tremors and movement problems, and as the disease progresses, it can cause difficulty speaking, swallowing, remembering and reasoning.

Recently, the goal of finding a cure for Parkinson’s has become more personal for me.

Since 2020, two of my aunties and an uncle have been diagnosed with Parkinson’s disease. It debilitated them, before they passed away.

In 1997, the neuronal protein alpha-synuclein was discovered as a key factor driving the development of Parkinson’s.

Early this century, neuroscientists discovered alpha-synuclein accumulates in the olfactory bulb in the nose, before spreading further back into the brain’s substantia nigra, a critical mid-brain structure, in which dopamine cells reside.

Disruption of the substantia nigra causes the movement problems associated with Parkinson’s.

But the first symptom of Parkinson’s is typically the loss of the sense of smell, which affects about 95 percent of people with the disease.

We hope one day people will be able to go to the doctor and be diagnosed earlier, from the loss of the sense of smell (and therefore access therapy earlier) so they won’t have to wait until they have other signs of Parkinson’s, such as movement problems.

In 2024, my research group, in collaboration with colleagues at the Max Planck Institute in Frankfurt, fulfilled our dream of building a full three-dimensional anatomical map of the olfactory system.

It was a world first, made possible through people generously gifting their bodies after they die to the human body bequest programme, and their brains to the Neurological Foundation Human Brain Bank.

We have also received intergenerational financial support from families who want long-term research into a cure for Parkinson’s.

This helped us develop the 3D model of the olfactory system, which has advanced our research.

In donated brains with no symptoms of Parkinson’s, we can now identify if harmful alpha-synuclein proteins are present in a person’s olfactory system. If they are, this indicates they might have developed Parkinson’s had they lived longer.

We have gone out to the community and asked New Zealanders with and without Parkinson’s disease if they would allow us to take a biopsy from the roof of their nose.

From this tissue, we have cultured cells, grown them into neurons, so we can test new drugs that might reduce alpha-synuclein. Drug testing is ongoing on our lab-grown brain cells.

We are also investigating the use a type of drug called PROTACs, which helps break down and remove harmful proteins from the brain.

The ultimate goal is to detect Parkinson’s early in the olfactory system, before the rest of the brain is affected.

We could then use a drug that clears alpha-synuclein from the olfactory system, reducing the burden of disease.

Any treatment we develop for the nose could also be useful for treating more advanced Parkinson’s in the brain.